Early exposure to a high fat diet produces metabolic and behavioral alterations associated to hippocampal neuroinflammation and impaired neurogenesis in C57BL/6 mice

VINUESA A; POMILIO C; PAVÍA P; MENAFRA M; BRITES F; BONAVENTURA M; LUX-LANTOS V; BEAUQUIS J; SARAVIA F

Frauenchiemsee

Workshop; Route 28 Summits in Neurobiology; 2014

Route 28 Summits in Neurobiology

Background Intake of hypercaloric diets and sedentarism have profoundly increased in the last decades, leading to a rising incidence of metabolic disorders including obesity, pre-diabetes, type two diabetes and metabolic syndrome. At the same time, these morbidities constitute major risk factors for neurodegenerative disorders such as Alzheimer?s disease (AD), which has itself a growing impact in modern societies where life expectancy has become greater. Several studies report that insulin resistance, impaired insulin signaling and inflammation promote cognitive impairment and contribute to alterations in the central nervous system, playing an essential role in the development of AD pathology. Aims - Establish in our hands a murine model of high fat diet (HFD) induced moderate obesity. - Study the effect effect of a high fat diet as a risk factor and potential enhancer of neurodegeneration. - Assess the behavioral profile of HFD mice and characterize possible central alterations in limbic structures associated, in terms of inflammatory response, neural activity and neurogenic ability. - Explore the molecular mechanisms involved in the interaction of both metabolic and neurodegenerative pathologies. Methods C57BL/6 male mice were given either a control diet CD (12% Kcal from fat) or a high fat diet HFD (45% kcal from fat) during 18 weeks since a week post weaning. Body weight and food consumption was registered weekly and behavioral tests were performed by the end of the treatment, from the 15th week onwards in a suitable room within housing facilities. Trunk blood, brain, liver and pancreas where rapidly extracted after decapitation. Determination of lipids, glucose and pancreatic insulin was done after a 6 hour fast.